Everolimus plus bevacizumab is an effective first-line treatment for patients with advanced papillary variant renal cell carcinoma: Final results from a phase II trial.

Abstract

BACKGROUND:

We previously reported on a phase 2 study of everolimus plus bevacizumab across various nonclear cell renal cell carcinoma (nccRCC) histologies and observed encouraging activity among patients with papillary RCC (pRCC) and unclassified RCC (uRCC) with a major papillary component. We subsequently expanded the study to enroll additional patients with pRCC variants.

METHODS:

Everolimus plus bevacizumab was administered at standard doses until disease progression or intolerance to therapy. The primary endpoint was the 6-month progression-free survival (PFS) rate; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Correlative analyses included next-generation sequencing (NGS) from tumor and germline across >341 genes of interest.

RESULTS:

In addition to 19 patients with pRCC variants in the original cohort, 20 patients with similar features were enrolled on the expansion cohort (uRCC with papillary features [n = 24], pRCC [n = 14], and translocation-associated RCC with papillary features [n = 1]). Among 37 evaluable patients, the 6-month PFS rate was 78%, the median PFS was 13.7 months (95% CI, 10.8-16.4 months), and the ORR was 35%. With a median follow-up of 17.6 months, the median OS was 33.9 months (95% CI, 23.3-71.9). Tolerance was consistent with prior reports for everolimus plus bevacizumab. NGS results (n = 33) identified responses in patients with a wide spectrum of genomic alterations, including ARID1A, FH, and MET mutations.

CONCLUSION:

The expansion cohort results confirm robust activity of everolimus plus bevacizumab in metastatic pRCC variants, supporting this regimen as a standard option for this patient population.

• Authors: Darren R Feldman, Yasser Ged, Chung-Han Lee, Andrea Knezevic, Ana M Molina, Ying-Bei Chen, Joshua Chaim, Devyn T Coskey, Samuel Murray, Satish K Tickoo, Victor E Reuter, Sujata Patil, Han Xiao, Jahan Aghalar, Arlyn J Apollo, Maria I Carlo, Robert J Motzer, Martin H Voss
• Journal: Cancer (Cancer) Vol. 126 Issue 24 Pg. 5247-5255 (12 15 2020) ISSN: 1097-0142 [Electronic] United States
• PMID: 32975815 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2020 American Cancer Society.

Chemical References

• ARID1A protein, human
• DNA-Binding Proteins
• Transcription Factors
• Bevacizumab
• Everolimus
• MET protein, human
• Proto-Oncogene Proteins c-met
• Fumarate Hydratase

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Bevacizumab (administration & dosage, therapeutic use)
• Carcinoma, Renal Cell (drug therapy, genetics, pathology)
• DNA-Binding Proteins (genetics)
• Everolimus (administration & dosage, therapeutic use)
• Female
• Fumarate Hydratase (genetics)
• High-Throughput Nucleotide Sequencing
• Humans
• Kidney Neoplasms (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Mutation
• Proto-Oncogene Proteins c-met (genetics)
• Sequence Analysis, DNA
• Survival Analysis
• Transcription Factors (genetics)
• Treatment Outcome